{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:24:05Z","timestamp":1787883845512,"version":"build-2784847793"},"reference-count":61,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,3,16]],"date-time":"2025-03-16T00:00:00Z","timestamp":1742083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Intervertebral disc degeneration (IVDD) is a primary contributor to low back pain, posing significant social and economic burdens. Increasing evidence shows that obesity contributes to IVDD, yet the underlying mechanisms remain elusive. Here, we firstly revealed a causal correlation between obesity and IVDD via a two\u2010sample mendelian randomization analysis and identified fatty acid\u2010binding protein 4 (FABP4) as the potential regulator to associate IVDD and obesity. Elevated FABP4 expression promoted extracellular matrix (ECM) disequilibrium and angiogenesis to exacerbate IVDD progression. Genetically knocking out or pharmacologically inhibiting FABP4 in high\u2010fat diet\u2010induced mice alleviated IVDD. Mechanistically, obesity activated the mammalian target of rapamycin complex 1 (mTORC1), which upregulated FABP4 expression, leading to the accumulation of advanced glycation end\u2010products (AGEs) in intervertebral disc tissue. AGEs further activated the NF\u2010\u03baB signalling pathway, exacerbating ECM degradation and neovascularization. Conversely, rapamycin\u2010mediated inhibition of mTORC1 suppressed FABP4 expression in nucleus pulposus cells (NPCs), alleviating IVDD in\u00a0vivo. Collectively, our findings reveal a critical role of the obesity\u2010induced mTORC1\u2010FABP4 axis in ECM degradation and angiogenesis during IVDD progression. Targeting FABP4 may represent a promising therapeutic strategy for IVDD in obese individuals.<\/jats:p>","DOI":"10.1111\/cpr.70021","type":"journal-article","created":{"date-parts":[[2025,3,16]],"date-time":"2025-03-16T22:59:02Z","timestamp":1742165942000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Targeting\n                    <scp>FABP4<\/scp>\n                    to Inhibit\n                    <scp>AGEs<\/scp>\n                    \u2010\n                    <scp>RAGE<\/scp>\n                    \/\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    Signalling Effectively Ameliorates Nucleus Pulposus Dysfunction and Angiogenesis in Obesity\u2010Related Intervertebral Disc Degeneration"],"prefix":"10.1111","volume":"58","author":[{"given":"Lin","family":"Han","sequence":"first","affiliation":[{"name":"Department of Orthopedic 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